Prenatal exposure to a cannabinoid receptor agonist does not affect sensorimotor gating in rats

Bortolato, Marco; Frau, Roberto; Orrù, Marco; Casti, Alberto; Aru, Gian Nicola; Fà, Mauro; Manunta, Mario; Usai, A; Mereu, Giampaolo; Gessa, Gian Luigi

doi:10.1016/j.ejphar.2005.12.017

Cited by 10 publications

(6 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In agreement with this idea, we found that treatment with 'typical' antipsychotic drugs, which antagonize D 2 -type dopamine receptors, normalize CSF anandamide levels in schizophrenic patients (Giuffrida et al, 2004). The possibility that endogenous anandamide may act as a downstream signal regulating dopaminergic transmission is further supported by animal experiments showing that the anandamide reuptake inhibitor AM404 attenuates certain behavioral effects exerted by D 2 -type receptor agonists, such as motor hyperactivity, whereas the CB 1 antagonist rimonabant exacerbates such effects (Bortolato et al, 2006;Fegley et al, 2004;Giuffrida et al, 1999).…”

Section: Discussionsupporting

confidence: 72%

Anandamide levels in cerebrospinal fluid of first-episode schizophrenic patients: Impact of cannabis use

Leweke

Giuffrida

Koethe

et al. 2007

Schizophrenia Research

214

172

View full text Add to dashboard Cite

Background: Previous studies have shown that cerebrospinal fluid (CSF) from schizophrenic patients contains significantly higher levels of the endogenous cannabinoid anandamide than does CSF from healthy volunteers. Moreover, CSF anandamide levels correlated inversely with psychotic symptoms, suggesting that anandamide release in the central nervous system (CNS) may serve as an adaptive mechanism countering neurotransmitter abnormalities in acute psychoses. In the present study we examined whether cannabis use may alter such a mechanism. Methods: We used liquid chromatography/mass spectrometry (LC/MS) to measure anandamide levels in serum and CSF from firstepisode, antipsychotic-naïve schizophrenics (n = 47) and healthy volunteers (n = 81). Based on reported patterns of cannabis use and urine Δ 9 -tetrahydrocannabinol (Δ 9 -THC) tests, each subject group was further divided into two subgroups: 'low-frequency' and 'high-frequency' cannabis users (lifetime use ≤5 times and N20 times, respectively). Serum Δ 9 -THC was investigated to determine acute use and three patients were excluded from the analysis due to detectable Δ 9 -THC levels in serum. Results: Schizophrenic low-frequency cannabis users (n = 25) exhibited N 10-fold higher CSF anandamide levels than did schizophrenic high-frequency users (n = 19, p = 0.008), healthy low-frequency (n = 55, p b 0.001) or high-frequency users (n = 26, p b 0.001). In contrast, no significant differences in serum anandamide levels were found among the four subgroups. CSF anandamide levels and disease symptoms were negatively correlated in both user groups. Conclusions:The results indicate that frequent cannabis exposure may down-regulate anandamide signaling in the CNS of schizophrenic patients, but not of healthy individuals. Thus, our findings suggest that alterations in endocannabinoid signaling might be an important component of the mechanism through which cannabis impacts mental health.

show abstract

Section: Discussionsupporting

confidence: 72%

Anandamide levels in cerebrospinal fluid of first-episode schizophrenic patients: Impact of cannabis use

Leweke

Giuffrida

Koethe

et al. 2007

Schizophrenia Research

214

172

View full text Add to dashboard Cite

show abstract

“…These results can explain the findings reported in the literature that cannabinoid agonists increase (Stanley-Cary et al 2002), decrease (Nagai et al 2006;Schneider and Koch 2002), or have no effect (Bortolato et al 2005;Bortolato et al 2006a;Bortolato et al 2006b;Mansbach et al 1996;Martin et al 2003) on PPI. Furthermore, corticosteroid effects of cannabinoid agonists on PPI elucidated here may be the mechanism by which chronic cannabinoid treatment in pubertal rats produces changes in adult PPI (Schneider and Koch 2003), since chronic corticosterone treatment has been shown to similarly impair PPI (Ingram et al 2005;Stevens et al 2001).…”

Section: Discussionsupporting

confidence: 46%

“…PPI is decreased in rats by drugs that induce psychosis in people, such as amphetamine (Curzon and Decker 1998;Mansbach et al 1988) or phencyclidine (PCP) (Curzon and Decker 1998), although the effects of these compounds or cannabinoids on PPI in humans are inconsistent (Kedzior and Martin-Iverson 2006;Quednow et al 2004;Swerdlow et al 2002;Swerdlow et al 2003). PPI effects of cannabinoids in rats are also unclear with no effects (Bortolato et al 2005;Bortolato et al 2006a;Bortolato et al 2006b;Mansbach et al 1996;Martin et al 2003), increases (Stanley-Cary et al 2002) and decreases (Nagai et al 2006;Schneider and Koch 2002) being reported.…”

Section: Introductionmentioning

confidence: 95%

Corticosteroid dependent and independent effects of a cannabinoid agonist on core temperature, motor activity, and prepulse inhibition of the acoustic startle reflex in Wistar rats

2011

View full text Add to dashboard Cite

show abstract

“…Oral administration of THC to pregnant rats did not change the auditory startle response of the offspring at adulthood (Hutchings et al 1991). More recent studies confirmed this early finding by showing that prenatal cannabinoid exposure did not affect startle magnitude and sensorimotor gating in the offspring tested at 40, 60, and 80 days of age (Bortolato et al 2006). Together, these studies suggest that prenatal exposure to cannabis derivatives does not affect reflex reactivity to environmental stimuli in the offspring.…”

Section: Long-term Behavioral Consequences Of Maternal Cannabis Exposurementioning

confidence: 65%

Developmental consequences of perinatal cannabis exposure: behavioral and neuroendocrine effects in adult rodents

et al. 2010

View full text Add to dashboard Cite

RationaleCannabis is the most commonly used illicit drug among pregnant women. Since the endocannabinoid system plays a crucial role in brain development, maternal exposure to cannabis derivatives might result in long-lasting neurobehavioral abnormalities in the exposed offspring. It is difficult to detect these effects, and their underlying neurobiological mechanisms, in clinical cohorts, because of their intrinsic methodological and interpretative issues.ObjectivesThe present paper reviews relevant rodent studies examining the long-term behavioral consequences of exposure to cannabinoid compounds during pregnancy and/or lactation.ResultsMaternal exposure to even low doses of cannabinoid compounds results in atypical locomotor activity, cognitive impairments, altered emotional behavior, and enhanced sensitivity to drugs of abuse in the adult rodent offspring. Some of the observed behavioral abnormalities might be related to alterations in stress hormone levels induced by maternal cannabis exposure.ConclusionsThere is increasing evidence from animal studies showing that cannabinoid drugs are neuroteratogens which induce enduring neurobehavioral abnormalities in the exposed offspring. Several preclinical findings reviewed in this paper are in line with clinical studies reporting hyperactivity, cognitive impairments and altered emotionality in humans exposed in utero to cannabis. Conversely, genetic, environmental and social factors could also influence the neurobiological effects of early cannabis exposure in humans.

show abstract

Prenatal exposure to a cannabinoid receptor agonist does not affect sensorimotor gating in rats

Cited by 10 publications

References 21 publications

Anandamide levels in cerebrospinal fluid of first-episode schizophrenic patients: Impact of cannabis use

Anandamide levels in cerebrospinal fluid of first-episode schizophrenic patients: Impact of cannabis use

Corticosteroid dependent and independent effects of a cannabinoid agonist on core temperature, motor activity, and prepulse inhibition of the acoustic startle reflex in Wistar rats

Developmental consequences of perinatal cannabis exposure: behavioral and neuroendocrine effects in adult rodents

Contact Info

Product

Resources

About